Bioactive constituents from the edible seaweed <i>Halymenia hawaiiana</i> (Rhodophyta)

The marine macroalga, <i>Halymenia hawaiiana</i>, holds significant commercial potential due to its culinary uses among various ethnic groups in Hawaiʻi and its success in aquaculture. To investigate the chemical components and potential medicinal properties of <i>H. hawaiiana</i>. Dried, ground <i>H. hawaiiana</i> was sequentially extracted with three solvents: ethyl acetate, methanol, and <i>n</i>-butanol. Chromatographic procedures were sequentially applied, leading to the isolation of several compounds. Structure determination of these compounds was performed using spectroscopic methods. The isolated compounds were then assessed through several <i>in vitro</i> assays. A total of 11 compounds were isolated and identified: two nucleosides (<b>1</b> and <b>2</b>), a cytosine analog (<b>3</b>), five saturated long-chain fatty acids (<b>4</b>–<b>8</b>), cholesterol (<b>9</b>), and two of its derivatives (<b>10</b>–<b>11</b>) were isolated. Compounds <b>10</b> and <b>11</b> displayed promising antimicrobial activity against <i>Staphylococcus aureus</i>, both exhibiting MIC values of 8 μg/mL, and methicillin-susceptible <i>S. aureus</i>, with MIC values of 32 and 64 μg/mL, respectively. Furthermore, using a cell culture model, compounds <b>9</b>, <b>10</b>, and <b>11</b> exhibited significant anti-inflammatory effects as indicated by their inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production, with IC₅₀ values ranging from 50.2 to 60.8 µM. These compounds also effectively inhibited the generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) in RAW 264.7 mouse macrophage cells with IC₅₀ values of 55–73.7 µM without inducing cytotoxicity. Compounds <b>9–11</b> also exhibited mild cytotoxicity against the non-small cell lung cancer cell line A549, with compound <b>10</b> eliciting the strongest response (IC₅₀ 86.1 µM). This study uncovered a diverse array of constituents from <i>H. hawaiiana</i>. Notably, compounds <b>10</b> and <b>11</b>, which feature peroxide side chains, show significant promise as lead compounds for the development of novel anti-inflammatory and antimicrobial agents.